title: Nanoceria extend photoreceptor cell lifespan in tubby mice by modulation of apoptosis/survival signaling pathways.
abstract: Cerium oxide nanoparticles, nanoceria, are inorganic antioxidants that have catalytic activities which mimic those of the neuroprotective enzymes superoxide dismutase and catalase. We have previously shown that nanoceria preserve retinal morphology and prevent loss of retinal function in a rat light damage model. In this study, the homozygous tubby mutant mouse, which exhibits inherited early progressive cochlear and retinal degeneration, was used as a model to test the ability of nanoceria to slow the progression of retinal degeneration. Tubby mice were injected systemically, intracardially, with 20 μl of 1mM nanoceria in saline, at postnatal day 10 and subsequently at P20 and P30 whereas saline injected and uninjected wild type (or heterozygous tubby) served as injected and uninjected controls, respectively. Assays for retinal function, morphology and signaling pathway gene expression were performed on P34 mice. Our data demonstrate that nanoceria protect the retina by decreasing Reactive Oxygen Species (ROS), up-regulating the expression of neuroprotection-associated genes; down-regulating apoptosis signaling pathways and/or up-regulating survival signaling pathways to slow photoreceptor degeneration. These data suggest that nanoceria have significant potential as global agents for therapeutic treatment of inherited retinal degeneration and most types of ocular diseases.
authors.affiliation: Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK73104, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Kong
authors.forename: Xue
authors.initials: X
authors.lastname: Cai
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhou
authors.forename: Lily L
authors.initials: LL
authors.lastname: Wong
authors.forename: Ajay S
authors.initials: AS
authors.lastname: Karakoti
authors.forename: Sudipta
authors.initials: S
authors.lastname: Seal
authors.forename: James F
authors.initials: JF
authors.lastname: McGinnis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D002563:Cerium / Q000008:administration & dosage*; D004596:Electroretinography; D051379:Mice; D018345:Mice, Knockout; D053758:Nanoparticles / Q000008:administration & dosage*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000502:physiology; D011506:Proteins / Q000235:genetics; D017382:Reactive Oxygen Species; D012162:Retinal Degeneration / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D011506:Proteins; D017382:Reactive Oxygen Species; C098988:Tub protein, mouse; D002563:Cerium; C030583:ceric oxide